LH Dynamics in Overweight Girls with Premature Adrenarche and Slowly Progressive Sexual Precocity

We have characterized a variant group of sexually precocious girls who presented diagnostic challenges that provided an opportunity to test hypotheses about pubertal pathophysiology. They met current criteria for sexual precocity, with breast and pubic hair development before 8 years of age [1–3]. However, they differed from girls with typical central precocious puberty (also termed complete, true, or gonadotropin-dependent premature puberty) because they had slowly progressive precocious breast development [4–6], were overweight, and had premature adrenarche (SPPOPA). Their early morning LH serum levels were also persistently prepubertal during the initial observation period. About one-third of girls with central precocity are overweight [7], about half have premature adrenarche (PA) [6], although it causes pseudoprecocity independently of true puberty [8], and only about 10% have early morning LH levels in the prepubertal range [9]. Thus, our SPPOPA group presented an uncommon, but not rare, combination of findings.Their peripubertal adiposity and hyperandrogenism suggested that they were at risk of developing polycystic ovary syndrome (PCOS), a hyperandrogenic anovulation disorder that is often accompanied by obesity [10]. Obesity potentially predisposes to the development of PCOS by causing premenarcheal LH excess that is mediated by peripubertal hyperandrogenemia [11–13]. PA, a mild form of adrenal hyperandrogenism, potentially poses increased risk for the development of PCOS, particularly in obese and African-American or Hispanic girls [10, 14, 15].The diagnostic challenge was to determine whether SPPOPA girls had early activation of the neuroendocrine-gonadal axis that ordinary testing failed to capture, whether their thelarche was due to adiposity-related peripheral estrogen formation [16], or whether they simply had pseudothelarche due to adipomastia. If they had adipomastia or estrogen excess of peripheral origin, one would expect LH dynamics to be suppres